CASE REPORT

The effect of calpain 3 deficiency on the pattern of muscle degeneration in the earliest stages of LGMD2A

M Vainzof¹, F de Paula¹, A M Tsanaclis², M Zatz¹

¹ Human Genome Research Centre, Department of Biology, IBUSP, University of São Paulo, São Paulo, Sao Paulo - CEP, 05508–900, SP Brazil
² Department of Pathology, FMUSP, University of São Paulo

Correspondence to:
Correspondence to:
Dr M Vainzof, Human Genome Research Centre, Department of Biology, IB, University of São Paulo, Rua do Matão 106, Cidade Universitária, Sao Paulo - CEP, 05508–900, SP Brazil;
mvainzof{at}usp.br

Limb girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the calpain 3 gene. In a large family affected by LGMD2A with four severely affected members, three additional asymptomatic relatives had very high serum creatine kinase concentrations. All were homozygous for the R110X mutation and showed a total absence of calpain 3 in the muscle. Histological analysis of muscle in these three rare preclinical cases showed a consistent but unusual pattern, with isolated fascicles of degenerating fibres in an almost normal muscle. This pattern was also seen in one patient with early stage LGMD2A who had a P82L missense mutation and a partial deficiency of calpain 3 in the muscle, but was not seen in early stage patients affected by other forms of LGMD. These findings suggest that a peculiar pattern of focal degeneration occurs in calpainopathy, independently of the type of mutation or the amount of calpain 3 in the muscle.

Keywords: limb girdle muscular dystrophy; calpain 3; LGMD2A

Abbreviations: AD, autosomal dominant; AR, autosomal recessive; LGMD, limb girdle muscular dystrophy; NS, N-terminus domain I; SG, sarcoglycan

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